A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

Phase 2

Completed

• Conditions: Muscular Dystrophies; Genetic Diseases, Inborn; Muscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Muscular Dystrophy, Duchenne; Neuromuscular Diseases; Muscular Disorders, Atrophic
• Interventions: Drug: Placebo; Biological: CAP-1002

• Registration Number: NCT03406780
• Lead Sponsor: Capricor Inc.

Brief Summary

HOPE-2 is a double-blind clinical trial evaluating the safety and efficacy of a cell therapy called CAP-1002 in study participants with Duchenne Muscular Dystrophy (DMD). Non-ambulatory and ambulatory boys and young men who meet eligibility criteria will be randomly assigned to receive either CAP-1002 or placebo every 3 months for a total of 4 doses during a 12-month period.

Detailed Description

* Approximately 20 eligible study participants will be randomized to either CAP-1002 or placebo in a 1:1 ratio.

* The trial will include visits at Screening, Baseline/Day 1, Week 4, and Months 3, 6, 9, and 12 with IV infusions of CAP-1002 or placebo on Day 1 and Months 3, 6, and 9.

* Safety evaluations will include adverse events, concomitant medications, physical exam, vital signs, 12-lead ECG, and clinical laboratory testing.

* Efficacy will be evaluated by Performance of the Upper Limb, cardiac MRI, pulmonary function testing, North Star Ambulatory Assessment (ambulatory subjects only), strength testing, and quality of life.

* If trial data suggests an appropriate risk/benefit profile of CAP-1002, Capricor, upon the recommendation of the Data Safety Monitoring Board (DSMB), will introduce an open-label extension study to offer CAP-1002 to study participants who were randomized to placebo and completed all trial visits during the 12-month period.

Study Timeline

• Study First Submitted: 2018-01-15
• Study First Submitted QC: 2018-01-19
• Study First Posted: 2018-01-23
• Study Start: 2018-04-04
• Primary Completion: 2020-03-10
• Study Completion: 2020-03-10
• Status Verified: 2025-01
• Results First Submitted: 2025-01-31
• Results First Submitted QC: 2025-01-31
• Last Update Submitted: 2025-01-31
• Results First Posted: 2025-02-24
• Last Update Posted: 2025-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

1. Male participants at least 10 years of age at time of consent
2. Participants willing and able to provide informed consent to participate in the trial if >= 18 years of age, and assent with parental or guardian informed consent if < 18 years of age
3. Participants with diagnosis of DMD based on clinical and phenotypic manifestations consistent with DMD (e.g., family history of DMD, elevated creatine kinase, dystrophin muscle biopsy, calf pseudohypertrophy, Gowers' sign, and gait impairment before 7 years of age) with confirmatory genetic testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
4. Participants with performance of the Upper Limb entry item score 2-5
5. Participants if ambulatory, 10-meter walk/run velocity < 1 meter/second
6. Participants with loss of independent ambulation by 18th birthday (standing unassisted or ability to take, at most, several steps independently is not considered ambulation)
7. Participants who receiving standard of care therapy at an experienced, multidisciplinary, DMD center as evidenced by regular cardiac and pulmonary monitoring, systemic glucocorticoid treatment, and at-home range of motion exercises
8. Participants who received treatment with a systemic glucocorticoid is required for at least 12 months prior to randomization. The dose must remain stable for at least 6 months prior to randomization with the exception of either weight-based dose adjustment or a decrease in steroid dose of ≤ 10% for toxicity. For patients on chronic deflazacort, treatment with an equivalent dose of prednisone or prednisolone for a period of ≤ 30 days to bridge lack of availability of deflazacort during the 6 months prior to randomization is acceptable
9. Participants with current and up-to-date immunizations according to children and adolescent Centers for Disease Control immunization schedule, unless contraindicated, including the following: meningococcal and meningococcal B; tetanus, diphtheria & acellular pertussis (Tdap); and pneumococcal polysaccharide vaccinations
10. Participants with adequate venous access for parenteral IP infusions and routine blood collections in the judgement of the Investigator
11. Participants assessed by the Investigator as willing and able to comply with the requirements of the trial

Exclusion Criteria

1. Participants with Left Ventricular Ejection Fraction (LVEF) < 35%
2. Participants with elbow-flexion contractures > 30° in both extremities
3. Participants with Body Mass Index (BMI) > 45
4. Participants with documentation of exon 44 skip-amenable mutation(s) in the dystrophin gene
5. Participants with documentation of dystrophin deletion mutation(s) encompassing and limited to exons 3-7
6. Participants with percent predicted FVC (FVC%p) < 35%
7. Participants with inability to perform consistent FVC measurement within ±15% during paired testing at screening
8. Participants with risk of near-term respiratory decompensation in the judgment of the investigator, or the need for initiation of non-invasive ventilator support as defined by serum bicarbonate ≥ 29 mmol/L at screening
9. Participants with history of non DMD-related chronic respiratory disease requiring ongoing or intermittent treatment, including, but not limited to, asthma, bronchitis, and tuberculosis
10. Participants with acute respiratory illness within 30 days prior to screening
11. Participants with initiation of non-invasive ventilation within 30 days prior to screening, or the anticipated need to initiate non-invasive ventilation within the 12 months following screening
12. Participants with planned or anticipated thoracic or spinal surgery within the 12 months following randomization
13. Participants with planned or anticipated lower extremity surgery within the 12 months following randomization, if ambulatory
14. Participants with known hypersensitivity to Dimethyl Sulfoxide (DMSO) or bovine products
15. Participants with initiation of treatment with metformin or insulin within 3 months prior to randomization
16. Participants with initiation of treatment with an FDA-approved exon skipping therapy for the treatment of DMD within 24 months prior to randomization or dose adjustments to the therapy within 12 months prior to randomization with the exception of weight-based dose adjustments.
17. Participants who received treatment with Human Growth Hormone (HGH) within 3 months prior to randomization, unless on a stable dose (as determined by the site PI) for at least 24 months prior to randomization
18. Participants who received Treatment with idebenone within 3 months prior to randomization
19. Participants who received treatment with a cell therapy product within 12 months prior to randomization
20. Participants who received treatment with an investigational product within 6 months prior to randomization
21. Participants with history, or current use, of drugs or alcohol that could impair their ability to comply with participation in the trial
22. Participants with inability to comply with the investigational plan and follow-up visit schedule for any reason, in the judgment of the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients will receive a placebo solution via intravenous infusion every 3 months for a total of 4 doses.
CAP-1002	CAP-1002	Patients will receive 150 million Cardiosphere-derived Cells (CDCs) via intravenous infusion every 3 months for a total of 4 doses.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Functional Capacity as Assessed by the Mid-level (Elbow) Dimension Score of the Performance of Upper Limb (PUL) Version 1.2 at Month 12	Baseline, Month 12	Change from baseline in functional capacity as assessed by the mid-level (elbow) dimension of PUL version 1.2 at Month 12 expressed as percentile ranked change.; PUL 1.2 scale assesses motor performance in the upper limb for individuals with dystrophinopathies, primarily Duchenne Muscular Dystrophy (DMD). PUL 1.2 included 22 items. These include one entry item to define the starting functional level, and 21 items subdivided into: Shoulder Level (Question B to E; minimum score 0 and maximum score 16); Elbow Level (Question F to N; minimum score 0 and maximum score 34); Distal Level Dimension (Question O to V; minimum score 0 and maximum score 24). The total score range was from 0 to 74. For all items, the higher the score, the better the outcome. A negative change indicates worst the outcome.
Number of Participants Experiencing Acute Respiratory Decompensation	Baseline through Month 12	Acute respiratory decompensation was defined as an unexplained rapid deterioration of the participant's condition with increasing shortness of breath requiring oxygen supplementation.
Number of Participants With Hypersensitivity Reactions	Baseline through Month 12	Hypersensitivity reaction was defined as a clinical syndrome including, but not limited to, fever, leukocytosis, or rash with onset less than or equal to (\<=) 2 hours post-infusion and lasting less than (\<) 24 hours, in the absence of clinical signs of concomitant infection.
Number of Participants With All-cause Mortality	Baseline through Month 12	Number of participants who died due to any cause were reported.
Number of Participants With Serious Adverse Events (SAEs)	Baseline through Month 12	A SAE was defined as an AE that results in any of the following outcomes: Death; life-threatening adverse event; Inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product (IP) or Administration Procedure	Baseline through Month 12	TEAE was defined as an AE that was not present prior to the initiation of line placement procedure for the IP infusion or was present but worsened in intensity or frequency. The Investigator assessed the relationship (causality) of an AE to the investigational product and administration procedure.
Number of Participants With Immune Sensitization Syndrome	Baseline through Month 12	Immune sensitization syndrome is defined as a) clinical signs and symptoms that are consistent with systemic inflammation (e.g.,fever, leukocytosis, rash, arthralgia), with an onset \>=24 hours after infusion of the investigational product, in the absence of clinical signs of concomitant infection, and b) an elevation of anti-Human Leukocyte Antigen (anti-HLA) antibodies against the Donor-Specific Antibody (DSA) cells, which is detected \<=30 days after the onset of syndrome, that meets the following criteria: i) 2000 mean fluorescence intensity if mean fluorescence intensity is \<=1000 at baseline, or ii) \>=2 times the baseline value.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With TEAEs and Severity of TEAEs	Baseline through Month 12	TEAE was defined as an AE that was not present prior to the initiation of line placement procedure for the IP infusion or was present but worsened in intensity or frequency. Severity of TEAEs were determined by following criteria:: Mild (Grade 1): Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required; Moderate (Grade 2): Mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required; Severe (Grade 3): Marked limitation in activity, some assistance usually required; medical intervention/therapy required and often requiring hospitalization or prolongation of hospitalization; Life-Threatening or Disabling (Grade 4): Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required; hospitalization, prolongation of hospitalization, or hospice care; Fatal (Grade 5): death.
Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9	Baseline, Months 3, 6, and 9	Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 expressed as percentile ranked change.; PUL 1.2 scale assesses motor performance in the upper limb for individuals with dystrophinopathies, primarily DMD. PUL 1.2 included 22 items. These include one entry item to define the starting functional level, and 21 items subdivided into: Shoulder Level (Question B to E; minimum score 0 and maximum score 16); Elbow Level (Question F to N; minimum score 0 and maximum score 34); Distal Level Dimension (Question O to V; minimum score 0 and maximum score 24). The total score range was from 0 to 74. For all items, the higher the score, the better the outcome. A negative change indicates worst the outcome.
Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12	Baseline, Months 6 and 12	Change from baseline in regional systolic LV wall thickening (anterior, lateral, inferior, septal) expressed as percentile ranked change, as assessed by cardiac MRI at Months 6 and 12.

Trial Locations

Locations (9)

University of California, Davis; 🇺🇸 Sacramento, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Nemours Children's Hospital; 🇺🇸 Orlando, Florida, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

University of Massachusetts Medical Center; 🇺🇸 Worcester, Massachusetts, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Children's Hospital Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States